UC-NRLF 


35    DOS 


THE  APPLICATION  OF  VICTOR  MEYER'S 

ESTERIFICATION    LAW    TO    NEIGH- 

BORING-XYLIC    ACID    AND    ITS 

REDUCED   DERIVATIVES 


BY 


RALPH   WILLIAM  HUFFERD 

A.  B.  Washington  University,  1915 
M.  A.  University  of  Illinois,  1917 


THESIS 

Submitted  in  Partial  Fulfillment  of  the 

Requirements  for  the 

Degree  of 

DOCTOR  OF  PHILOSOPHY      * 

IN  CHEMISTRY  »..; 

IN 

THE  GRADUATE  SCHOOL 
OF  THE 

UNIVERSITY  OF  ILLINOIS 
1920 

Reprinted  from  the  Journal  of  the  American  Chemical  Society 
Vol.  XLIII.     No.  4.     April,  1921. 


I  Reprinted  from  the  Journal  of  the  American   Chemical  Society 
Vol.  XLIII.      No.  4.      April,  1921.] 


[CONTRIBUTION  FROM  THE  CHEMICAL  LABORATORY  OF  THE  UNIVERSITY  OF  ILLINOIS.] 

THE  APPLICATION  OF  VICTOR  MEYER'S  ESTERIFICATION  LAW 
TO  2,6-XYLIC  ACID  AND  ITS  REDUCED  DERIVATIVES.1 

BY  RALPH  W.  HUFFERD  WITH  WILLIAM  A.  NOYES. 

Received  January  25,   1921. 

Historical. 

Victor  Meyer  found  that  aromatic  acids  with  both  ortho  positions 
filled  are  not  to  be  esterified  by  the  usual  method.  The  work  of  himself 
and  his  pupils2  led  Meyer  to  formulate  the  rule  which  is  known  as  Victor 
Meyer's  Esterification  Law.  It  states,  "When  in  a  substituted  benzoic 
acid  the  two  hydrogen  atoms  adjacent  to  the  carboxyl  group  are  sub- 
stituted by  such  groups  as  Br,  NO2,  CH3,  etc.,  the  acid  is  not  esterifiable 
by  alcohol  and  hydrochloric  acid." 

Meyer  explained  this  difficulty  of  esterification  by  advancing  the 
theory  of  steric  hindrance.  He  believed  that  the  groups  adjacent  to 
the  carboxyl  covered  it  up  so  as  to  prevent  free  collision  between  the 
alcohol  molecule  and  the  carboxyl  group.  A  strong  argument  in  favor 
of  this  explanation  is  the  difference  in  behavior  toward  esterification 
of  di-0r//w-substituted  benzoic  acids  and  similarly  substituted  acids 
with  the  carboxyl  removed  from  the  ring  by  at  least  one  atom.  Sym- 
metrical trimethyl-benzoic  acid  obeys  the  law  but  both  mesityl-glyoxylic 
acid  and  mesityl-acetic  acid  esterify  readily.  In  fact,  even  the  ortho 
hydrogen  atoms  in  benzoic  acid  are  credited  with  some  blanketing  effect, 
since  it  was  found  that  phenylacetic  acid  is  more  easily  esterified  than  is 
benzoic  acid  itself. 

Wegscheider3  advanced  some  data  which  are  in  accordance  with  Meyer's 
rule,  but  he  objected  to  Meyer's  steric  hindrance  explanation  and  de- 
clared that  the  effect  is  due  to  a  state  of  tension  within  the  molecule. 

The  most  antagonistic  critic  of  the  steric  hindrance  idea  is  M.  A.  Rosan- 

1  An  abstract  of  a  thesis  submitted  by  Ralph  W.  Hufferd  in  partial  fulfilment  of 
the  requirements  for  the  degree  of  Doctor  of  Philosophy  in  the  Graduate  School  of  the 
University  of  Illinois. 

2  Meyer,  et.  al.,  Ber.  27,r510,  1585,  3146  (1894);  28,  182,  1254,  2776,  3197,  3219 
(1895);  29,  830,  839,  1397  (1896);  Z.  physik.  Chem.,  24,  219,  221  (1897). 

8  Wegscheider,  Monatsch.f.  Chem.,  18,  643  (1897);  Ber.,  28,  2535  (1895). 

444257 


926  ,  RALPH  w.  HUFPERD  WITH  WILLIAM  A.  NOYUS, 

off.1  He  and  his  co-workers  carried  out  several  esterification  experiments 
in  which  the  acid  was  heated  with  ethyl  alcohol  in  a  sealed  tube  without 
the  addition  of  any  mineral  acid.  Most  of  the  trials  were  made  at  the 
temperature  of  boiling  aniline,  and  for  a  much  longer  time  than  is  ordi- 
narily employed  for  esterifications.  The  results  of  this  work  led  Rosanoff 
to  make  the  statement,  "Di-ortho  substituted  aromatic  acids,  which  are 
generally  assumed  to  be  unesterifiable,  can  be  esterified  quantitatively 
at  higher  ter&peratures,  or  even,  by  prolonged  warming,  at  the  tempera- 
ture of  the  water-bath."  He  restated  the  Ksterification  Law  to  read, 
"Aromatic  acids  with  one  or  both  positions  next  to  the  carboxyl  occupied 
by  substituting  groups,  combine  with  alcohols  more  slowly,  though  to 
no  less  extent,  than  acids  otherwise  substituted."  He  further  stated, 
"Our  dynamic  study  proves  that  Victor  Meyer's  hypothesis  of  steric 
hindrance  is  untenable  and  thus,  for  the  present,  reduces  the  Esterifica- 
tion Law  to  the  rank  of  an  empirical  rule  of  no  theoretical  and  limited 
practical  value.  The  hypothesis  that  the  low  rate  of  esterification  is 
due  to  the  mechanical  interference  of  groups  or  atoms  situated  near 
the  carboxyl  in  the  molecule  is  untenable." 

W.  L.  Prager2  followed  the  methods  of  Rosanoff  and  arrived  at  a  sim- 
ilar conclusion. 

Theoretical. 

From  the  preceding  resume  of  the  literature  it  is  evident  that  there 
are  two  distinct  points  of  view  from  which  a  reaction  may  be  considered. 
Meyer  studied  the  qualitative  aspect  to  draw  his  conclusions,  which  he 
couched  in  quantitative  terms.  Rosanoff,  following  the  belief  of  Bredig3 
that  everything  chemical  must  be  considered  quantitatively  from  the 
dynamic  side,  considers  it  useless  to  distinguish  between  difficult  and 
easy  reactions.  According  to  him,  no  rule  of  any  great  value  could  be 
deduced  from  such  a  grouping,  and  no  knowledge  could  be  gained  as  to 
molecular  structure  by  correlating  such  reactions. 

Although  Rosanoff  refuses  to  give  any  consideration  to  Meyer's  explana- 
tion of  the  hindrance  being  due  to  a  blanketing  effect,  he  very  willingly 
accepts  Wegscheider's  idea  that  it  is  due  to  a  condition  of  strain  within 
the  molecule  induced  by  the  substituting  groups. 

Without  accepting  entirely  either  of  the  above  explanations  but  with  a 
firm  conviction  that  organic  structures  can  be  deduced  from  cumulative 
evidence  of  a  qualitative  nature  and  cannot  be  assigned  numerical  values, 
the  present  work  was  undertaken. 

If  Meyer's  explanation  is  correct,  the  following  results  can  be  predicted: 

2,6-Xylic  acid  (I)  should  not  esterify. 

1  Rosanoff,  THIS  JOURNAL,  30,  1895  (1908). 

2  Prager,  ibid.,  30,  1908  (1908). 

3  Bredig,  Z.  physik.  Chem.,  21,  154  (1896). 


ESTERIFICATION   LAW  APPLIED    TO    2,6-XYIJC   ACID,    ETC.  927 


COOH 


(I.)  (II.)  (HI.)  (IV.) 

Hexahydro-2,0-xylic  acid  (II),  lias  very  much  the  same  grouping  as 
xylic,  but  is  purely  aliphatic  in  nature.  Its  three  isomers  would  be  ex- 
pected to  give  different  results,  which  might  be  predicted  as  follows: 
The  one  with  the  grouping,  1,  should  not  esterify.  The  second,  with  the 
grouping  2,  would  be  expected  to  esterify  with  very  poor  yields.  The 
third,  which  would  have  the  grouping  3,  would  probably  esterify  easily. 

I  i  I 

— C— CHS  — C— CH,  CHs— C— 

I  I  I 

— C— CO2H  — C— COaH  — C— COjH 

I  I  ! 

— C— CH3  CH2— C—  CH3— C— 

|     1.  |     2.  |     3. 

AI  tetrahydro-2,6-xylic  acid  (III),  in  which  the  carboxyl  is  in  the  same 
plane  with  only  one  methyl  group,  would  not  be  expected  to  esterify 
with  as  much  difficulty  as  xylic  acid  itself. 

Ai,5  dihydro-2,6-xylic  acid,  IV,  of  which  the  linkage  of  the  carboxyl 
group  is  the  same  as  in  xylic  acid,  should  not  esterify  easily. 

The  A3  tetrahydro-2,6-xylic  acids  from  their  similarity  to  the  hexa- 
hydro  acids  would  be  expected  to  behave  in  much  the  same  manner  as 
these. 

Discussion  of  Results. 

The  results  obtained  in  this  study  of  2,6-xylic  acid  and  its  reduction 
products  agree  quite  well  with  the  predictions  based  on  Victor  Meyer's 
Ksterification  Law. 

Predicted  Found. 

Acid.  esterification.  %. 

Benzoic Quantitative  96 

Xylic None  3.5 

AI  tetrahydro-xylic Fair  41 

A3  tetrahydro-xylic Poor  to  good  75 

Ai,5  dihydro-xylic None  47 

Hexahydro-xylic Poor  to  good  52 

From  this  comparison  of  the  results  obtained  with  those  predicted 
it  is  evident  that  the  Esterification  Law  cannot  be  applied  quantitatively. 
However,  the  results  offer  strong  evidence  combating  Rosanoff's  state- 
ment that  the  law  is  of  little  practical  value. 

It  is  clear,  as  Victor  Meyer  claimed,  that  ortho  substituents  interfere 
with  the  esterification  of  aromatic  acids,  though  Rosanoff  is  also  right 


928  RALPH    W.    HUKFERD   WITH    WILLIAM   A.    NOYtfS. 

in  saying  that  they  do  not  absolutely  prevent  esterification.  Physical 
chemistry  has,  as  yet,  given  no  satisfactory  explanation  of  why  certain 
reactions  take  place  slowly  while  others  go  rapidly.  Until  it  can  do  this, 
the  idea  of  steric  hindrance  seems  to  be  useful  as  a  superficial  explanation, 
at  least,  for  the  results  which  have  been  found. 

It  seems  possible  that  the  mechanism  of  the  reactions  studied  by  Rosan- 
off,  in  which  he  used  only  mixtures  of  an  acid  with  alcohol,  is  different 
from  that  of  the  reactions  in  the  presence  of  hydrochloric  acid  as  a  catalytic 
agent.  Rosanoff's  reaction  may  be  a  direct  substitution  of  ethyl  for 
hydrogen.  In  Victor  Meyer's  studies  and  ours  there  is  probably  an 
intermediate  addition  reaction.  A  study  of  velocities  in  the  presence 
and  absence  of  hydrochloric  acid  might  throw  light  on  this  question. 

Experimental. 

The  methods  of  preparation  of  the  materials  used  in  this  work  are  in 
general  those  employed  by  one  of  us  in  previous  work.1 

Mesitylene. — In  the  preparation  of  mesitylene  the  same  proportions  of  acetone 
and  sulfuric  acid  were  used,  but  in  each  run  2300  g.  of  acetone  were  condensed.  The 
yield  of  carefully  purified  mesitylene  was  16  to  19%  of  that  calculated  for  the  acetone 
used. 

Aceto-mesitylene. — Aceto-mesitylene  was  prepared,  starting  with  255  g.  quan- 
tities of  mesitylene.  Half  an  hour  after  adding  the  aluminum  chloride  the  whole  mix- 
ture was  poured  into  a  large  flask  of  cracked  ice.  The  carbon  disulfide  layer  was  sep- 
arated and  the  residue  extracted  with  500  cc.  of  carbon  disulfide.  The  disulfide  was 
distilled  off  from  the  combined  extracts  and  the  residue  distilled  through  a  Skinner 
column.2  In  order  to  obtain  a  product  which  does  not  darken  on  standing,  it  was  found 
necessary  to  redistil  under  diminished  pressure.  The  yield,  boiling  at  122-122.5°  at 
19  mm.,  was  300  g. 

Oxidation  of  Aceto-mesitylene. — By  using  a  mechanical  stirrer  it  was  found 
possible  to  oxidize  90  g.  of  aceto-mesitylene  at  a  time  in  a  5-liter  balloon-flask.  The 
flask  was  cooled  with  tap  water  so  as  to  keep  the  temperature  below  40°.  To  the 
aceto-mesitylene  were  added  27  g.  of  sodium  hydroxide  and  1000  cc.  of  water;  180  g. 
of  potassium  permanganate  was  added  in  portions  of  10  to  15  g.  After  about  half  of  the 
permanganate  had  been  added,  900  cc.  of  water  was  poured  in  and  the  remainder  of 
the  permanganate  added  as  before.  This  process  took  about  3  hours. 

The  solution  was  then  stirred  for  another  hour  and  the  flask  transferred  to  the 
steam-bath  and  heated  with  occasional  shaking  until  all  of  the  permanganate  was  de- 
stroyed. To  the  hot  solution  was  carefully  added  225  cc.  of  50%  sulfuric  acid,  and  the 
mixture  returned  to  the  steam-bath  for  half  an  hour.  This  oxidized  the  mesityl-gly- 
oxylic  acid  present, CeHaCCHs^COCOaH,  to  trimethyl-benzoic  acid.  It  was  then  cooled 
under  the  tap  and  145  g.  of  sodium  hydroxide  added.  When  the  hydroxide  was  all  in 
solution  the  flask  was  returned  to  the  stirrer  and  500  cc.  of  water  added.  230. 5  g.  of 
permanganate  was  added  in  four  portions  at  half -hour  intervals.  Stirring  was  continued 
for  3  hours.  The  flask  was  transferred  to  the  steam-bath  and  heated  until  all  of  the 
permanganate  was  destroyed.  To  the  hot  solution  were  added  700  cc.  of  50%  sulfuric 
acid  and  enough  sodium  hydrogen  sulfite  to  destroy  the  oxides  of  manganese.  The  hot 
solution  was  quickly  filtered  by  suction  and  the  filtrate  discarded.  The  precipitate  was 

1  Noyes,  Am.  Chem.  J,,  20,  789  (1896);  22,  1  (1898). 

2  Skinner,  THIS  JOURNAL,  39,  2718  (1917). 


ESTERIFICATION   LAW   APPUED   TO   2,6-XYUC  ACID,    ETC.  929 

dissolved  in  strong  ammonium  hydroxide,  the  solution  cooled  and  shaken  out  with 
ether,  and  then  filtered  by  suction.  The  acid  was  thrown  out  by  adding  sulfuric  acid. 
It  was  filtered  hot  and  washed  with  hot  water. 

The  yield  of  dry  acid  varied  from  70  to  95  g.  in  a  great  number  of  runs  in  which 
there  was  no  apparent  difference  in  procedure.  It  is  very  slightly  soluble  in  hot  or 
cold  ether  and  insoluble  in  hot  chloroform. 

Esterification  of  Dimethyl  Terephthalic  Acid. — The  yield  of  the  acid  ester  was 
consistently  over  97%,  thus  indicating  quantitative  prevention  of  esterification  of  the 
protected  carboxyl. 

Preparation  of  the  Amido  Acid. — The  ester  was  dissolved  in  about  twice  its  weight 
of  strong  ammonium  hydroxide,  the  solution  cooled  under  the  tap,  and  ammonia  gas 
passed  in  for  3  or  4  days.  The  temperature  was  held  at  about  45°  during  this  time. 
The  crystalline  ammonium  salt  was  then  filtered  off,  sucked  dry,  washed  with  cold, 
strong  ammonium  hydroxide  and  then  allowed  to  stand  covered  with  ether  for  several 
hours.  The  ether  was  sucked  off  and  the  powdered  salt  partially  dissolved  in  hot 
water.  Hydrochloric  acid  was  added  with  stirring  and  the  mixture  cooled  under  the 
tap  for  2  hours.  The  amide  was  filtered  off,  washed  with  cold  water,  sucked  dry,  and 
then  suspended  in  ether  and  let  stand  overnight.  The  ether  was  sucked  off  and  the 
amide  washed  on  the  filter  with  ether.  The  ammoniacal  mother  liquors  were  aerated 
and  then  acidified.  The  precipitated  dimethyl  terephthalic  acid  was  dried,  esterified, 
and  again  treated  with  ammonium  hydroxide.  The  total  yield  of  amide  was  about 
75%  of  the  calculated  amount  for  the  acid  used.  It  is  insoluble  in  ether,  benzene,  and 
chloroform,  and  soluble  in  hot  water,  from  which  it  crystallizes  on  cooling. 

Preparation  of  £-Iodo-2,6-Xylic  Acid. — The  amide  was  carried  through  to  the 
iodo  acid  without  isolating  any  intermediate  product.  15.5  g.  of  the  finely  powdered 
amide  was  ground  into  60  cc.  of  10%  sodium  hydroxide  solution  which  had  been  cooled 
to  zero  in  an  ice-salt  mixture;  120  cc.  more  of  the  cold  hydroxide  solution  was  slowly 
added  with  constant  grinding.  A  cold  solution  of  5  cc.  of  bromine  in  100  cc.  of  10% 
sodium  hydroxide  solution  was  slowly  added  with  grinding.  A  clear  solution  was  ob- 
tained. It  was  transferred  to  a  flask,  20  cc.  of  50%  sodium  hydroxide  solution  added, 
and  immersed  in  a  boiling  water-bath  for  25  minutes.  It  was  then  cooled  under  the 
tap  to  about  50°,  transferred  to  a  large  beaker  standing  in  tap  water,  and  50%  sulfuric 
acid  added  until  the  precipitate  which  formed  had  redissolved;  50  cc.  more  of  the  acid 
were  added  and  the  solution  filtered  to  remove  a  small  quantity  of  dark-colored  solid 
matter. 

The  filtrates  from  three  such  runs  were  combined  in  a  3-liter  flask  and  cooled  to 
— 2°.  A  solution  of  60  g.  of  potassium  nitrite  in  75  cc.  of  water  was  added  in  4  portions 
at  5-minute  intervals.  This  was  allowed  to  stand  for  15  minutes  during  which  time  a 
heavy  yellow  precipitate  formed.  The  mixture  was  then  poured  into  a  5-liter  flask 
containing  150  g.  of  potassium  iodide  and  250  cc.  of  25%  sulfuric  acid,  and  heated  on 
the  steam-bath  with  occasional  shaking  until  effervescence  ceased.  The  flask  was 
then  cooled  under  the  tap  and  sodium  hydrogen  sulfite  added  until  the  free  iodine  was 
destroyed.  The  iodo  acid  was  filtered  off  and  thoroughly  washed. 

Preparation  of  2,6-Xylic  Acid. — The  iodo  acid  was  dissolved  in  50  cc.  of  strong 
ammonium  hydroxide,  care  being  taken  to  prevent  the  solution  from  becoming  hot. 
A  few  grams  of  zinc  dust  was  added  and  the  flask  shaken  under  the  tap  for  a  few  minutes. 
After  about  half  an  hour  more  zinc  and  ammonium  hydroxide  were  added  and  the  flask 
placed  on  the  steam-bath  in  such  a  position  that  a  temperature  of  about  70°  would 
be  maintained,  and  let  stand  overnight.  The  zinc  was  filtered  off  by  suction  and  the 
acid  thrown  out  by  adding  hydrochloric  acid.  The  xylic  acid  was  filtered  off  and  the 
filtrate  twice  extracted  with  ether.  The  residue  from  evaporating  off  the  ether  was 


930  RALPH   W.   HUFFERD   WITH   WILLIAM   A.    NOYBS. 

combined  with  the  acid  on  the  filter  and  the  whole  distilled  at  17  mm.  It  distilled  be- 
tween 155°  and  160°  and  melted  at  114°.  When  crystallized  from  hot  water  it  melted 
sharply  at  1 16°.  The  yield  in  several  runs  was  consistently  over  65%  of  that  calculated 
for  the  amide  used. 

The  acid  does  not  distil  well  with  steam. 

Reduction  of  2,6-Xylic  Acid. — Six  g.  of  xylic  acid  was  dissolved  in  150  cc.  of  dry 
iso-amyl  alcohol  in  a  1-liter  round-bottom  flask  specially  constructed  to  carry  a  large 
reflux  condenser,  a  mercury-seal  motor-driven  stirrer,  and  a  tube  for  admitting  pieces 
of  sodium.  The  solution  was  heated  to  boiling  with  a  free  flame,  the  stirrer  started, 
and  30  g.  of  sodium  added  from  time  to  time  in  pieces  of  about  a  gram  each.  More 
alcohol  was  added  as  needed  to  prevent  crust  formation.  When  all  of  the  sodium  was 
used  up  the  flame  was  removed  and  the  hot  solution  poured  with  stirring  into  a  large 
beaker  containing  a  liter  of  water. 

A  second  batch  of  6  g.  was  treated  with  alcohol  and  sodium  in  the  same  manner 
and  poured  into  the  beaker  with  the  first.  The  procedure  was  repeated  with  two  more 
6-g.  lots  of  the  acid.  The  alcohol  layer  from  the  whole  lot  was  placed  in  a  large  distilling 
flask  with  a  piece  of  porous  plate,  a  liter  of  water  added,  and  the  mixture  boiled  until 
about  500  cc.  remained  in  the  flask.  The  aqueous  layer  was  then  poured  in  and  the 
distillation  continued.  More  water  was  added  as  needed  to  distil  out  the  amyl  alcohol. 
Frothing  marked  the  removal  of  the  last  of  the  alcohol. 

The  alkaline  solution  was  cooled  and  poured  into  a  large  beaker  cooled  with  ice- 
water.  Hydrochloric  acid  was  added  to  excess  and  the  solution  twice  extracted  with 
ether .  The  strong  smelling  oil  obtained  by  evaporating  off  the  ether  was  dissolved  in 
warm  ligroin  to  get  rid  of  water,  the  water  being  sucked  off  through  a  pipet  drawn  to 
a  fine  tip.  The  ligroin  was  evaporated  off  and  the  residue  placed  in  a  vacuum  desiccator 
over  phosphoric  anhydride.  After  3  hours  the  residue  was  dissolved  in  amyl  alcohol 
and  divided  into  3  portions,  each  of  which  was  treated  as  before  with  30  g.  of  sodium. 
The  acid  was  recovered  as  after  the  first  reduction  and  again  reduced  in  3  portions. 
After  the  alcohol  was  removed  following  the  third  reduction,  the  alkaline  solution  was 
extracted  with  ether  before  acidifying.  The  residue,  after  extracting  and  evaporating 
oft  the  ether,  was  distilled  at  23  mm.  Almost  all  of  it  came  over  at  154-6°.  The  dis- 
tillate weighed  19  g. 

It  was  dissolved  in  carbonate  solution  and  extracted  with  ether.  The  acid  was 
divided  into  5  portions  by  means  of  partial  precipitation  with  hydrochloric  acid  and 
shaking  out  with  ether. 

A3Tetrahydro-2,6-Xylic  Acid. — When  the  third  and  fourth  fractions  from  above 
were  let  stand  for  3  weeks  a  heavy  growth  of  crystals  formed.  These  were  separated 
from  the  liquid  acids  and  washed  several  times  with  low-boiling  petroleum  ether.  They 
were  then  dissolved  in  carbonate  solution,  the  solution  extracted  once  with  ether  and 
twice  with  petroleum  ether,  the  last  traces  of  the  petroleum  ether  aerated  out,  and  the 
solution  cooled  in  ice  and  acidified  with  dil.  sulfuric  acid.  The  unsaturated  acid  came 
out  as  an  oil  which  immediately  solidified.  When  pressed  out  on  filter  paper,  it  melted 
at  85-7°.  It  was  then  distilled  at  28  mm.,  coming  over  at  158°  to  160°.  After  solution 
in  carbonate  solution  and  reprecipitation,  a  product  was  obtained  which  melted  at 
93.4°. 

Analyses.     Calc.  for  CsHi4O2:  C,  70.09;  H,  9.15.     Found:  C,  69.77;  H,  9.07. 

Bromine  was  added  and  the  resulting  compound  analyzed. 

Calc.  for  C9Hi4O2Br2:  Br,  50.88.     Found:  50.43. 

Treatment  with  1 : 1  sulfuric  acid  destroyed  the  acid. 

Heating  for  24  hours  with  50%  potassium  hydroxide  did  not  change  either  the 
melting  point  or  the  refractive  index  of  the  acid. 


ESTERIFICATION  LAW  APPLIED  TO   2,6-XYLIC  ACID,   ETC.  931 

Since  the  Ai  acid  is  known  and  is  different  from  this  acid,  the  above  data  were 
considered  as  sufficient  to  place  the  new  acid  as  the  A3  tetrahydro-2,6-xylic  acid,  w9D6, 
1.4462;  d*5,  0.9553. 

Employing  the  Lorentz-Lorenz  formula,  the  molecular  refractivity  is  MV  =  43.06. 

Hexahydro-2,6-Xylic  Acid. — The  remaining  fractions  from  the  reduction  of  the 
xylic  acid  together  with  the  washings  from  the  tetrahydro  acid  were  freed  from  ether 
and  ligroin  and  stirred  into  20  cc.  of  hydrobromic  acid,  saturated  at  0.  The  mixture 
was  covered  and  set  away  in  the  ice  box  for  24  hours.  It  was  then  let  stand  at  room 
temperature  for  12  hours.  Crushed  ice  and  20  cc.  of  ice-water  were  added  and  the  solid 
acid  separated  from  the  solution.  It  was  washed  with  cold  water  and  suspended  in 
sodium  hydrogen  carbonate  solution  in  a  flask  fitted  with  a  stirrer  and  surrounded  with 
ice.  A  kilogram  of  3%  sodium  amalgam  was  added,  and  carbon  dioxide  was  passed 
in  for  12  hours.  Enough  water  was  added  from  time  to  time  to  keep  the  bicarbonate 
in  solution.  The  mercury  was  removed  and  the  reduced  acid  thrown  out  with  sulfuric 
acid.  It  was  extracted  with  ether  and  the  ether  aerated  off.  It  was  then  treated  as 
before  with  hydrobromic  acid,  followed  by  amalgam.  The  sodium  hydrogen  carbonate 
solution  was  cooled  with  a  freezing  mixture  and  treated  with  permanganate  solution 
until  the  addition  of  a  little  2%  permanganate  solution  gave  a  color  which  held  for 
one  minute.  Some  sodium  hydrogen  sulfite  was  added  and  the  reduced  acid  thrown 
out  with  sulfuric  acid.  More  sodium  hydrogen  sulfite  was  stirred  in  until  all  color  was 
destroyed.  The  acid  was  filtered  off  and  redissolved  in  sodium  carbonate  solution,  the 
solution  cooled  and  permanganate  added  until  a  permanent  pink  was  obtained.  The 
acid  was  precipitated,  filtered  off,  and  washed  thoroughly.  It  melted  at  74.5-75.3°. 

The  acid  was  distilled  with  steam  with  conductivity  water  and  collected  in  3  frac- 
tions. In  order  to  ascertain  the  degree  of  purity  of  the  material,  the  melting  point  and 
refractive  index  of  each  fraction  were  determined. 

Melting  point.  86 

Fraction.  °  C.  n  D 

Original  74 . 5-75 .3  1 . 4372 

1  75.6  1.4371 

2  75.5-75.8  1.4369 

3  75.5-75.8  1.4366 
Residue  74 . 5-75  1 . 4370 

Fractions  2  and  3  were  used  for  conductivity  and  density  work;  na£,  1.4371;  d86, 
0.9454;  MD,  43.28  (Lorentz-Lorenz). 

Preparation  of  Ai-Tetrahydro-2,6-Xylic  Acid. — Two  g.  of  the  hexahydro  acid  was 
cautiously  treated  in  an  open-bomb  tube  with  3  g.  of  phosphorus  pentachloride,  and  then 
warmed  for  a  few  minutes  in  the  steam-bath.  It  was  cooled,  0.657  cc.  of  bromine  was 
added,  and  the  tube  sealed.  It  was  heated  in  the  steam-bath  for  3  hours,  cooled,  the 
tube  opened  and  the  contents  poured  into  ice- water.1  After  stirring  for  15  minutes, 
the  bromo-acid  chloride  was  taken  out  with  ether,  the  ether  solution  dried  with  sodium 
sulfate,  the  ether  aerated  off,  and  the  residue  dissolved  in  glacial  formic  acid  and  refluxed 
for  an  hour.  It  was  allowed  to  stand  overnight,  during  which  time  the  bromo  acid 
crystallized  in  its  characteristic  flakes.  The  crystals  were  filtered  off  and  the  filtrate 
diluted  and  extracted  with  ether.  The  ether  was  removed  and  the  residue  and  crystals 
refluxed  for  10  hours  with  alcoholic  potash.  Most  of  the  alcohol  was  distilled  off,  sul- 
furic acid  was  added,  and  the  unsaturated  acid  taken  out  with  ether.  The  ether  was 

1  It  is  interesting  to  note  that  this  bromo  acid  chloride  is  very  stable,  not  being 
affected  by  stirring  overnight  with  0.1  N  alkali,  and  resisting  heating  to  boiling  in 
25%  potassium  hydroxide  solution,  thus  agreeing  well  with  the  findings  of  Sudborough, 
J.  Chem.  Soc.,  67,  601  (1895). 


932  RALPH   W.    HU1MRD   WITH   WIU.IAM   A.   NOYE£. 

removed  and  the  residue  distilled  with  steam.  After  several  hours  cooling  under  the 
tap  most  of  the  acid  crystallized  from  the  distillate.  It  was  extracted  with  ether 
and  again  steam-distilled,  using  conductivity  water.  The  part  coming  over  in  the 
middle  of  the  distillation  crystallized  when  cooled  overnight.  The  yield  was  2  g.  from 
6  g.  of  the  hexahydro  acid.  It  melted  at  91-91.5°;  d»,  0.8625;  w9D5  1.4700;  MD,  49.87 
(Lorentz-Lorenz).  It  is  slowly  soluble  in  petroleum  ether. 

i,2-Dibromo-hexahydro-2,6-Xylic  Acid. — A  weighed  amount  of  the  AI  tetrahydro 
acid  was  dissolved  in  chloroform  and  treated  with  less  than  the  theoretical  quantity  of 
bromine.  It  was  decolorized  in  3  hours.  More  bromine  was  added  and  the  solution 
let  stand  overnight.  The  chloroform  and  excess  bromine  were  aerated  off  with  dried 
air,  leaving  a  white  solid  which  dissolved  with  difficulty  in  ligroin.  This  substance 
had  no  sharp  melting  point  but  melted  with  decomposition  at  128-32°  when  heated 
quickly. 

0.165  g.  of  the  dibromo  acid  when  titrated  with  0.1  N  alkali  used  15.3  cc.;  that 
calculated  for  neutralizing  the  carboxyl  is  5.2  cc.  This  result  indicated  that  not  only 
was  the  carboxyl  neutralized  but  both  bromine  atoms  were  removed  in  the  titration. 

The  solution  from  the  titration  was  acidified  with  sulfuric  acid  and  extracted  with 
ether.  A  very  little  nitric  acid  was  added  and  the  solution  titrated  with  0.1  N  silver 
nitrate  solution;  9.9  cc.  was  required,  whereas  the  calculated  amount  was  10.4  cc. 

Ai,6-Dihydro-2,6-Xylic  Acid. — The  dibromo  acid  was  heated  for  half  an  hour  on 
the  steam-bath  with  a  slight  excess  of  0.1  N  alkali.  The  solution  was  cooled  and  ex- 
tracted with  ether.  An  excess  of  sulfuric  acid  was  added  and  the  solution  again  ex- 
tracted. The  ether  was  removed  in  vacua,  leaving  a  syrupy  acid  which  was  almost 
entirely  soluble  in  a  cold  sodium  carbonate  solution.  It  did  not  give  a  test  for  halogen. 
The  carbonate  solution  was  extracted,  acidified,  and  again  extracted.  The  ether  was 
removed  as  before  and  the  residue  titrated  with  0.0161  N  alkali.  There  was  some 
insoluble  residue.  This  was  removed  with  ether  and  the  acid  recovered  by  acidifying 
and  extracting.  The  extract  was  dissolved  in  ligroin  by  warming  with  a  fairly  large 
volume.  On  evaporating  the  ligroin  in  vacuo  a  white  solid  was  obtained.  It  melted 
slowly  before  the  beaker  had  reached  room  temperature.  The  acid  was  titrated  and 
again  gave  an  appreciable  quantity  of  residue  even  though  the  alkaline  solution  was 
boiled. 

These  facts  together  with  a  changing  refractive  index  showed  plainly  that  either 
the  method  did  not  yield  a  pure  dihydro  acid  or  that  the  acid  was  continually  going 
over  into  another  substance  by  the  action  of  the  alkaline  solution  or  the  air. 

The  acid  was  distilled  in  an  all-glass  apparatus.  It  came  over  at  155-60°  at  28  mm. 
The  distillate  was  a  liquid  which  on  standing  in  vacuo  became  of  the  consistency  of 
vaseline.  It  dissolved  completely  in  sodium  hydrogen  carbonate  solution,  reduced 
permanganate  very  rapidly,  decolorized  bromine  in  chloroform,  and  was  very  slightly 
soluble  in  petroleum  ether  even  when  warmed  for  some  time. 

Analysis.    Calc.  for  C9H12O2:  C  71.01;  H,  7.95.     Found:  C,  70.70;  H,  8.11. 

Esterification  of  2,6-Xylic  Acid. 

The  method  employed  for  the  esterification  of  all  of  the  acids  was  to 
dissolve  the  acid  in  a  large  excess  of  dry  methyl  alcohol  containing  3  or  4% 
of  hydrochloric  acid,  and  reflux  for  4  hours  after  boiling  became  vigorous. 
The  larger  part  of  the  alcohol  was  then  boiled  off  through  a  Skinner 
column.  No  free  acid  could  be  detected  in  the  distillate  from  any  run. 
The  residue  in  the  flask  was  cooled  and  diluted.  Sodium  carbonate 
solution  was  added  to  strongly  alkaline  reaction  and  the  solution  twice 


ESTKRIFICATION  LAW  APPLIED  TO   2,6-XYLIC  ACID,   ETC.  933 

extracted  with  ether,  the  ether  solution  being  washed  twice  with  water 
and  the  water  returned  to  the  solution.  The  solution  was  then  shaken 
out  twice  with  ligroin,  acidified  with  sulfuric  acid  and  extracted  twice 
with  ether.  The  ether  was  washed  as  before  with  water,  evaporated 
off  in  a  beaker  which  was  then  placed  in  a  vacuum  desiccator  over  phos- 
phorus pentoxide  and  allowed  to  stand  overnight.  It  was  weighed, 
the  contents  taken  out  with  absolute  ether  and  again  weighed.  The 
difference  between  the  loss  in  weight  and  the  weight  of  the  sample  was 

recorded  as  the  amount  esterified. 

i  G.  2  G. 

Xylic  acid 1.000  1.000 

Alcohol 65  50 

HC1 2.6  1.8 

Xylic  acid  recovered 0.972  0.963 

Per  cent,  esterified 2.8  3.5 

Questioning  Rosanoff  s  view  but  hoping  to  get  some  of  the  iso-amy 
ester  by  direct  esterification,  we  made  the  following  run:  xylic  acid, 
3.6  g.;  iso-a.my\  alcohol,  b.  p.  131°,  100  cc.;  sulfuric  acid,  c.  P.,  96%,  2.5 
cc.;  time  refluxed,  64  hours;  xylic  acid  recovered,  3.4  g.;  esterification, 
5.5%. 

ESTERIFICATION  OF  2,6-Xvuc  ACIDS. 
20  g.  of  Methyl  Alcohol  Used  in  Each  Case. 

Acid 

Acid.  HC1.  recovered.       Esterified. 

G.  G.  G.  %. 

Hexahydro 0.901  0.66  0.433  51.9 

0.433  0.7  0.225  48.0 

AiTetrahydro 0.620  0.7  0.391  36.9 

0.421  0.7  0.250  40.6 

A3Tetrahydro 0.309  0.7  0.075  75.0 

Ai,6Dihydros 0.277  0.7  0.148  47.0 

*  The  recovered  dihydfo  acid  was  again  esterified  and  gave  30%  esterification. 
The  acid  was  recovered  a  second  time  and  esterified  to  the  extent  of  23%.  In  every 
case  both  the  ester  and  the  recovered  acid  gave  good  strong  tests  for  unsaturation. 
After  the  third  esterification  there  was  evidence  of  xylic  acid  in  the  recovered  acid.  To 
determine  if  the  acid  is  easily  oxidized  to  xylic  acid  it  was  heated  to  near  boiling  in  dis- 
tilled water  for  about  an  hour.  On  cooling,  xylic  acid  crystallized  out  and  the  test  for 
unsaturation  was  very  weak. 

Conductivities  of  2,6-Xylic  Acids. 

In  all  of  the  conductivity  work  the  solutions  were  made  up  by  weight 
at  25°.  All  measurements  were  made  at  25°.  The  cell  had  bright 
electrodes  and  was  standardized  against  potassium  chloride  and  checked 
against  pure  benzoic  acid,  giving  the  values  of  White  and  Jones.1  Aoo 
values  were  calculated  by  Ostwald's  rule.  No  correction  was  made  for 
the  water  used.  Conductivity  water:  7.0  X  10 ~7. 

1  White  and  Jones,  Am.  Chem.  J.,  44,  183  (1910). 


934  RALPH   W.   HUFFERD   WITH   WIIJJAM  A. 

V.              A.  a.  k. 

2,6-Xylic  Acid 128      92.53  0.2461     6.28  X  10 ~4 

512  160.5  0.4268    6.21  X  10~4 

1024  199.8  0.5314    5.88  X  10~4 

oo  376  

Hexahydro-2,6-Xylic  Acid 768      35 . 70  0 . 0952     1 . 30  X  10 ~5 

1024      41.07  0.1095     1.31  X  10~6 

oo  375  

^Telr aliy dro- 2,6-Xylic  Acid 768      62 . 59  0 . 1669    4 . 35  X  10 ~5 

1024      71.03  0.1894     4.32  X  10~5 

oo  375  

&zTetrahydro-2,6-Xylic  Acid 768      61 . 15  0. 1631     4. 14  X  10~5 

1024  69.92  0.1864     4. 17X10-* 

oo  375  

Summary. 

1.  The  method  of  preparation  of  2,6-xylic  acid  has  been  improved,  and 
its  degree  of  esterification  and  its  ionization  constant  have  been  deter- 
mined. 

2.  The  method  of  preparation  of  hexahydro-2,6-xylic  acid  has  been 
improved,   and  its  degree  of  esterification,  molecular  refractivity,   and 
ionization  constant  have  been  determined. 

3.  A  new  compound,  A3  tetrahydro-2,6-xylic  acid,  has  been  prepared, 
and  its  degree  of  esterification,  molecular  refractivity,  and  ionization 
constant  have  been  determined. 

4.  A  new  compound,    Ai,5  dihydro-2,6-xylic  acid,  has  been  prepared, 
and  its  degree  of  esterification  determined. 

5.  AI  Tetrahydro-2,6-xylic   acid  has  been  prepared,   and  its  degree 
of  esterification,   molecular  refractivity,   and  ionization  constant  have 
been  determined. 

6.  The  constants  of  the  acids  mentioned  and  the  percentages  of  esterifi- 
cation on  boiling  for  4  hours  with  methyl  alcohol  containing  4%  of  hydro- 
chloric acid  were  as  follows: 

Mol. 

Esterified.        refractivity.  k. 

Acid.  %.  L— L.  F=1024. 

2,6-Xylic 3.5             ...  5.88  X  10"4 

Hexahydro  Xylic 52  43.276  1.31  X  10~5 

AiTetrahydro  Xylic 41  49.870  4.32  X  lO"6 

A3Tetrahydro  Xylic 75  43.057  4.17  X  10~5 

Ai,6Diliydro  Xylic 47  ...  

7.  The  esterification  of  2,6-xylic  acid  on  boiling  with  methyl   alcohol 
containing  hydrochloric  acid  conforms  qualitatively  to  Victor   Meyer's 
law.     Esterification  proceeds  very  slowly. 

8.  The  esterification  of  the  hexahydro-2,6-xylic  acid  indicates  far  less 
steric  hindrance  than  occurs  with  the  corresponding  xylic  acid. 

9.  There  is  more  hindrance  to  the  esterification  of  the  AI  than  to  that 


ESTERIFICATION   LAW   APPLIED   TO   2,6-XYLIC   ACID,   ETC.  935 

of  the  A3  tetrahydro-2,6-xylic  acid.  This  is  decidedly  in  favor  of  the 
idea  of  steric  hindrance  as  the  structure  of  the  AI  acid  resembles  that  of 
the  xylic  acid  much  more  closely  than  does  that  of  the  A3  acid. 

10.     The  esterification  of  the  Ab5  dihydro-2,6-xylic  acid  is  less  favorable 
to  the  idea  of  steric  hindrance  as  being  merely  due  to  space  relations. 

URBANA,  ILL. 


VITA 

The  candidate  was  born  at  Chanute,  Kansas,  August  5, 
1892.  He  graduated  from  Washington  University,  St.  Louis, 
in  1915  with  the  A.  B.  degree,  and  obtained  the  M.  A.  degree 
at  the  University  of  Illinois  in  1917. 

While  at  the  University  of  Illinois  the  candidate  held  the 
appointments,  graduate  assistant,  assistant,  and  fellow. 


ACKNOWLEDGMENT 

The  writer  wishes  to  thank  Professor  Noyes  for  the  ever 
kindly  and  patient  aid  which  he  has  given  throughout  this 
work  both  as  to  the  actual  working  out  of  difficulties  and  as 
to  encouragement  at  times  when  it  was  so  badly  needed. 

He  also  wishes  to  thank  Professors  Adams  and  Kamm 
for  many  suggestions  which  were  of  great  value  to  him. 


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